title: A role for UDP-glucose glycoprotein glucosyltransferase in expression and quality control of MHC class I molecules.
abstract: UDP-glucose:glycoprotein glucosyltransferase 1 (UGT1) serves as a folding sensor in the calnexin/calreticulin glycoprotein quality control cycle. UGT1 recognizes disordered or hydrophobic patches near asparagine-linked nonglucosylated glycans in partially misfolded glycoproteins and reglucosylates them, returning folding intermediates to the cycle. In this study, we examine the contribution of the UGT1-regulated quality control mechanism to MHC I antigen presentation. Using UGT1-deficient mouse embryonic fibroblasts reconstituted or not with UGT1, we show that, although formation of the peptide loading complex is unaffected by the absence of UGT1, the surface level of MHC class I molecules is reduced, MHC class I maturation and assembly are delayed, and peptide selection is impaired. Most strikingly, we show using purified soluble components that UGT1 preferentially recognizes and reglucosylates MHC class I molecules associated with a suboptimal peptide. Our data suggest that, in addition to the extensively studied tapasin-mediated quality control mechanism, UGT1 adds a new level of control in the MHC class I antigen presentation pathway.
authors.affiliation: Departments of Immunobiology and Cell Biology, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06520-8011, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Pamela A
authors.initials: PA
authors.lastname: Wearsch
authors.forename: Yajuan
authors.initials: Y
authors.lastname: Zhu
authors.forename: Ralf M
authors.initials: RM
authors.lastname: Leonhardt
authors.forename: Peter
authors.initials: P
authors.lastname: Cresswell
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000235:genetics / Q000276:immunology*; D002460:Cell Line; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology*; D005964:Glucosyltransferases / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D006801:Humans; D026901:Membrane Transport Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D010455:Peptides / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D017510:Protein Folding
chemical_list: D015395:Histocompatibility Antigens Class I; D026901:Membrane Transport Proteins; D010455:Peptides; C107762:tapasin; D005964:Glucosyltransferases; C072423:mannosylglycoprotein 1,3-glucosyltransferase